Pharmacology, Toxicology and Environmental Health Commons^™

Effects Of Neonicotinoid Pesticide Exposure On Human Health: A Systematic Review., Andria M Cimino, Abee L Boyles, Kristina A Thayer, Melissa J. Perry

Environmental and Occupational Health Faculty Publications

BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure.

OBJECTIVE: This systematic review sought to identify human population studies on the health effects of neonics.

METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the …

Estimating Indoor Pm2.5 And Co Concentrations In Households In Southern Nepal: The Nepal Cookstove Intervention Trials, C. Chen, S. Zeger, P. Breysse, J. Katz, W. Checkley, F. Curriero, James Tielsch

Global Health Faculty Publications

High concentrations of household air pollution (HAP) due to biomass fuel usage with unvented, insufficient combustion devices are thought to be an important health risk factor in South Asia population. To better characterize the indoor concentrations of particulate matter (PM2.5) and carbon monoxide (CO), and to understand their impact on health in rural southern Nepal, this study analyzed daily monitoring data collected with DataRAM pDR-1000 and LASCAR CO data logger in 2980 households using traditional biomass cookstove indoor through the Nepal Cookstove Intervention Trial–Phase I between March 2010 and October 2011. Daily average PM2.5 and CO concentrations collected in area …

Nitrate From Drinking Water And Diet And Bladder Cancer Among Postmenopausal Women In Iowa., Rena R Jones, Peter J Weyer, Curt T Dellavalle, Maki Inoue-Choi, Kristin E Anderson, Kenneth P Cantor, Stuart Krasner, Kim Robien, Laura E Beane Freeman, Debra T Silverman, Mary H Ward

Exercise and Nutrition Sciences Faculty Publications

BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources and a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens.

OBJECTIVES: To investigate the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women.

METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) >10 years (N=15,577), we estimated average …

The Emergence Of Systematic Review In Toxicology, Martin L. Stephens, Kellyn Betts, Nancy Beck, Vincent Cogliano, Kay Dickersin, George Gray, +8 Additional Authors

Environmental and Occupational Health Faculty Publications

The Evidence-based Toxicology Collaboration hosted a workshop on “The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology,” on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts …

Effect Of An Improved Biomass Stove On Acute Lower Respiratory Infections In Young Children In Rural Nepal: A Cluster-Randomised, Step-Wedge Trial, James M. Tielsch, Joanne Katz, Subarna K. Khatry, Laxman Shrestha, Patrick N. Breysse, Scott L. Zeger, +5 Additional Authors

Global Health Faculty Publications

Background

Acute lower respiratory infections (ALRI) are an important cause of death in young children in low income countries. High concentrations of fine particulate matter (PM2.5) indoors caused by open burning of biomass are associated with risk of ALRI. However, improved biomass stoves reduce emissions and might reduce the incidence of lower respiratory illness. A cluster-randomised, step-wedge, community-based trial was conducted to estimate the eff ect that a change from open burning of biomass to improved biomass stoves could have on rates of ALRI in children younger than 36 months in a rural area of southern Nepal.

Methods

Households were …

Treatment Of Men For “Low Testosterone”: A Systematic Review, Samantha Huo, Anthony R. Scialli, Sean Mcgarvey, Elizabeth Hill, Buğra Tügertimur, Alycia Hogenmiller, Alessandra I. Hirsch, Adriane Fugh-Berman

Pharmacology and Physiology Faculty Publications

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation …

Brain Responses To Biological Motion Predict Treatment Outcome In Young Children With Autism, D. Yang, Kevin Pelphrey, D. Sukholdolsky, M. Crowley, E. Dayan, +6 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal …

Sensory Hypo-Excitability In A Rat Model Of Fetal Development In Fragile X Syndrome, Julia Berzhanskaya, Marnie Phillips, Jing Shen, Matthew Colonnese

Pharmacology and Physiology Faculty Publications

Fragile X syndrome (FXS) is characterized by sensory hyper-sensitivity, and animal models suggest that neuronal hyper-excitability contributes to this phenotype. To understand how sensory dysfunction develops in FXS, we used the rat model (FMR-KO) to quantify the maturation of cortical visual responses from the onset of responsiveness prior to eye-opening, through age equivalents of human juveniles. Rather than hyper-excitability, visual responses before eye-opening had reduced spike rates and an absence of early gamma oscillations, a marker for normal thalamic function at this age. Despite early hypo-excitability, the developmental trajectory of visual responses in FMR-KO rats was normal, and showed the …

Enhancing Access To Alcohol Use Disorder Pharmacotherapy And Treatment In Primary Care Settings: Adapt-Pc., Hildi J Hagedorn, Randall Brown, Michael Dawes, Eric Dieperink, Donald Hugh Myrick, Elizabeth M Oliva, Todd H Wagner, Jennifer P. Wisdom, Alex H S Harris

Health Policy and Management Faculty Publications

BACKGROUND: Only 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation …

Cross-Sectional Associations Between Exposure To Persistent Organic Pollutants And Leukocyte Telomere Length Among U.S. Adults In Nhanes, 2001-2002., Susanna D. Mitro, Linda S. Birnbaum, Belinda L. Needham, Ami R. Zota

Environmental and Occupational Health Faculty Publications

Background: Exposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL.

Objectives: We examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001-2002. Methods: We created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the …

Iarc Monographs: 40 Years Of Evaluating Carcinogenic Hazards To Humans, Neil Pearce, Aaron Blair, Paolo Vineis, Wolfgang Ahrens, Aage Andersen, Melissa J. Perry, +Several Additional Authors

Environmental and Occupational Health Faculty Publications

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.

Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process …

A Systematic Review And Meta-Regression Analysis Of Lung Cancer Risk And Inorganic Arsenic In Drinking Water., Steven H. Lamm, Hamid Ferdosi, Elisabeth K. Dissen, Ji Li, Jaeil Ahn

Epidemiology Faculty Publications

High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The …

An Exploratory Study Of Dog Park Visits As A Risk Factor For Exposure To Drug-Resistant Extra-Intestinal Pathogenic E. Coli (Expec)., Lubna N. Ahmed, Lance B. Price, Jay P. Graham

Environmental and Occupational Health Faculty Publications

Background

Extraintestinal pathogenic E. coli (ExPEC) are common causative agents of urinary tract infections in humans. Dogs have been found to harbor ExPEC. This study tested stool samples from dogs (n = 16), the shoes of dog park visitors (n = 16) and the shoes of controls (n = 16) for ExPEC. Phenotypic resistance of isolates was characterized.

Findings

ExPEC were present in one-third of the dog stool samples, 9% of the samples from the shoes of dog park visitors and 6% of control samples. Half of the ExPEC isolates were multi-drug resistant.

Discussion

The findings suggest that dogs may …

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …

Possible Pro-Carcinogenic Association Of Endotoxin On Lung Cancer Among Shanghai Women Textile Workers, H. Checkoway, J. I. Lundin, S. Costello, R. Ray, W. Li, E. A. Eisen, G. Astrakianakis, N. Seixas, Katie M. Applebaum, D. L. Gao, D. B. Thomas

Environmental and Occupational Health Faculty Publications

Background:

Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure.

Methods:

We updated a case–cohort study nested within a cohort of 267 400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989–2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure–response trends, adjusted for age and smoking, for cumulative …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Medicaid Managed Care Contracting For Childhood Lead Poisoning Prevention Services, Elizabeth Wehr, Sara J. Rosenbaum

Center for Health Policy Research

This study reports on provisions relating to childhood lead poisoning prevention services in Medicaid managed care contract documents (service agreements and requests for proposals, RFPS). The provisions were extracted from the managed care contracts data base of the Center for Health Policy Research of the George Washington University Medical Center. The data base was constructed and is updated as part of the Center's ongoing analytic studies.' As with other Center studies of the contract documents, this is a descriptive study of how state Medicaid agencies addressed a series of contracting issues at a specific point in time.* In brief, we …